Novel Approaches for Brain Drug Delivery System-Review

More documents

Recommendations

Info

International Journal of Pharma Research & Review, June 2013; 2(6):36-44 ISSN: 2278-6074low extra-tumoral interstitial drugconcentrations [15].Brain tumors may also disrupt BBB, butthese are also local and non homogeneousdisruptions [16].APPROACHES TO CNS DRUG DELIVERYBasically, two methods have been describedin the literature to actively enhance drugdelivery to the brain after systemicadministration: either opening/disruptionof the neuroprotective BBB by osmoticimbalance, ultrasound or vasoactivecompounds (e.g., bradykinin or P-glycoprotein inhibitors), or physiologicalstrategies aiming to use endogenoustransport mechanisms. While the firstmethod has the disadvantage that thoseneurons may be damaged (semi)-permanently due to unwanted bloodcomponents entering the brain [17-21]. Thephysiological strategies have a largepotential as discussed in several reviewpapers elsewhere [22]. As a thirdalternative (using a combination of aspectsof both methods), positive charge has alsobeen applied to compounds or drug carriersto quite effectively enhance the absorptivemediatedtransport across the BBB [23-24];however, a beneficial therapeutic windowof this basically toxic transport mechanismhas thus far not been established.To overcome the multitude of barriersrestricting CNS drug delivery of potentialtherapeutic agents, numerous drug deliverystrategies have been developed. Thesestrategies generally fall into one or more ofthe following categories: invasive, noninvasiveor miscellaneous techniques [27-29].The CNS drug delivery tree encompassingthe various possible strategies is shownbelow in the (Fig. 4).Fig. 4: Schematic representation of the different drug delivery approaches to the CNS.PHARMACEUTICAL TECHNOLOGY-BASEDSTRATEGIESThe technological strategies are essentiallynon-invasive methods of drug delivery tothe CNS and represent valuable approachesfor enhancing transcellular permeability oftherapeutic agents and biomacromoleculesacross the BBB. They are based on the useof nanosystems (colloidal carriers), mainlyliposomes and polymeric nanoparticleseven though other systems such as solidlipid nanoparticles, polymeric micelles anddendrimers are also being tried.An important requirement of the systemicintravenous use of these nanocarriers istheir ability to circulate in the bloodstreamfor a prolonged period of time. However,after intravenous administration, theyinteract with the reticuloendothelial system(RES) which removes them from the bloodstream.This process mainly depends on particlesize, charge and surface properties of thenanocarrier [25-26].To prevent the uptake by the RES, polyethylene glycol (PEG) coating or directchemical linking of PEG to the particlesurface provides relatively long plasmaSwatantra Bahadur Singh, IJPRR 2013; 2(6) 39
International Journal of Pharma Research & Review, June 2013; 2(6):36-44 ISSN: 2278-6074residence times.In fact, thesenanocarrierscan be taken up actively by carrier–mediated transport (CMT), receptormediatedendocytosis (RME) andadsorptive-endocytosis (AME) and hencereaches the cerebral parenchyma, or isdegraded within lysosomes leading to thedrug being released into the brain tissues.LiposomesLiposomes are small vesicles (usuallysubmicron-sized) comprising of one ormore concentric bilayers of phospholipidsseparated by aqueous compartments. It hasalso been suggested that liposomes couldenhance drug delivery to the brain acrossthe BBB. Although liposomes have beenreported to enhance the uptake of certaindrugs into the brain after intravenousinjection.Liposomes are sterically stabilized byattaching ligands to the surface of theliposomes [28-29].A recent application of transferrin surfaceconjugatedliposomes includes the deliveryof the anticancer drug 5- fluorouracil (5-FU)to brain. 5-FU is one of the most powerfulanticancer agents, but cannot reach aneffective concentration in the brain tumorcells when administered systemically.Modified liposomes have also been used forenhanced gene delivery to brain tumors.Fig. 5: Schematic representation of the different Pharmaceutical carriers for drugpenetration across the BBB.NanoparticlesNanoparticles (NPs) are solid colloidalparticles made up of polymeric materialsranging in size from 1-1000 nm. Thisdefinition includes both nanocapsules, witha core-shell structure (a reservoir system),and nanospheres (a matrix system). NPs areused as a carrier systems in which the drugis dissolved, entrapped, encapsulated,adsorbed or chemically linked to the surface[30].NPs possess the advantage of a high drugloading capacity and can provide protectionagainst chemical and enzymaticdegradation. Examples of syntheticpolymers used to prepare NPs are poly(alkylcyanoacrylate) (PACA), acryliccopolymers, poly(D,L-lactide-co-glycolide),and poly(lactide). NPs have also beenprepared from natural proteins (albuminand gelatin) and polysaccharides, starchand chitosan).Like liposomes, NPs are rapidly clearedfrom the blood following intravenousadministration. As carriers for drug deliveryto the brain, NPs need to be small (
Page 1 and 2: International Journal of Pharma Res
Page 3: International Journal of Pharma Res
Page 7 and 8: International Journal of Pharma Res
Page 9: International Journal of Pharma Res

Novel Approaches for Brain Drug Delivery System-Review

Create successful ePaper yourself

Delete template?

Save as template?